Cellular and Molecular Imaging

October, 2011

Molecular and cellular imaging techniques answer questions about  normal biochemical activities of cells and their molecules,  and how these are altered by disease, injury and their treatments, but they do so at a much higher resolution in space and time than do PET, SPECT and MRS.  Cellular and molecular imaging techniques use several types of light microscopes, and various types of “optical probes,” which are molecules that have been specially labeled to emit light of various wavelengths, to “contrast” the target cells of interest from other cells.

Molecular imaging, therefore, exploits specific molecules for image contrast. This refers to the ability to measure and characterize cellular and molecular activities in living animals or humans, or in their tissues, by using contrast to identify and follow actions of only the specifically labeled molecules. While “intravital” light microscopy—used to visualize live organisms—was developed more than 170 years ago, the development in recent times of many types of highly specialized light-emitting probes, advances in specialized light microscopes, and computerization have transformed the science of optical imaging.

There are two general types of intravital cellular imaging technologies: microscopic and macroscopic. Microscopic techniques are used to image molecules in tissues from humans and laboratory animals, and in live small laboratory animals. Macroscopic techniques are used in live small and a few large laboratory animals.

Intravital microscopic imaging is undertaken in tissue cultures from humans or animals, with tissues that have been biopsied or surgically removed; this imaging also can be undertaken in small laboratory animals to visualize the actions of labeled cells in a specific location. The cells of interest, whether being viewed in tissue culture or in small laboratory animals, are labeled with one of several types of light-emitting probes of differing wave lengths and visualized with one of several types of microscopes; each combination has specialized advantages.

Intravital macroscopic imaging differs from intravital microscopy in that macroscopic imaging is undertaken only in living laboratory animals, not in tissue cultures. Moreover, unlike microscopic imaging in live small animals where the image is confined to the exact location under view, intravital macroscopic imaging provides the capacity to visualize labeled light-emitting cells everywhere they are located within the animal’s body and anywhere these cells travel to within the body. Additionally, while macroscopic imaging is usually undertaken in small laboratory animals, it also can be used in a few large laboratory animals, such as sheep and pigs.

Both microscopic and macroscopic cellular imaging technologies utilize many of the same types of light-emitting probes to contrast the cells of interest from all other cells. Some can only show molecules located near the skin, while others can show molecules that are deeper within tissues.   The types of microscopes and probes used vary depending upon the scientific questions being asked and the locations of target cells. For instance, certain combinations of microscopes and probes are used to visualize a single labeled molecule in a cell to see what it does, while other combinations show how one molecule influences another. Opportunities with microscopic and macroscopic imaging span the range from whole animals, to whole organs, to single cells, and single molecules. 

In fact, there are myriad purposes for using molecular and cellular imaging techniques, but among some of the most common are the following.  The techniques reveal biochemical activities involved in the: architecture of a cell;  dynamic interactions between two cells or molecules, or among many cells or molecules;  gene expression (the production by a gene of its protein, which has evolved to carry out a specific function); cell division (proliferation of new healthy or cancerous cells); cell death;   assault and killing of cells by immune cells or infectious agents; processes of tissue integrity and tissue degeneration; wound healing; angiogenesis (formation of new blood vessels such as during brain development, or to supply brain tissues following a stroke, or to provide increased blood and its nutrients to fast-growing tumors);  gas exchange; cellular or molecular “trafficking”-such as the migration of immune cells into and within the brain in response to injury or infection; and to identify where, within a specific tissue, a particular molecular activity occurs. Imaging of these and other activities provides information about the normal development of cells and their biochemical activities, cells’ responses to attack or injury, and how therapies—such as drugs—alter the cells’ responses.